Human papillomavirus (HPV) is prevalent in the oral mucosa and may be involved in the etiology of oral squamous cell carcinoma. No study to date has evaluated HPV as a risk factor for oral cancer. The proposed research is a case-control of 65 patients registered at the University of Texas M.D. Anderson Cancer Center with previously untreated, histologically confirmed oral squamous cell carcinoma and 74 age-, sex- and race-matched controls. The cases and controls have been accrued, and medical history questionnaire data have been collected and automated. Collection of laboratory data concerning the prevalence of HPV and mutagen-induced chromosome breakage was recently completed. The measurement of the antibody response to HPV will be accomplished using HPV-derived synthetic peptides as antigens in an enzyme-linked immunoassay. The serologic response data and HPV prevalence and typing data will be evaluated as risk factors for oral cancer in univariate analysis. Data from self-administered risk factor questionnaires and mutagen-induced chromosome sensitivity data will be integrated with the HPV data. The results of the proposed study will provide a basis for larger prospective studies to evaluate HPV infection as a possible marker for tumor development.